Tissue adhesives and sealants have many potential medical applications, including wound closure, supplementing or replacing sutures or is staples in internal surgical procedures, preventing leakage of fluids such as blood, bile, gastrointestinal fluid and cerebrospinal fluid, adhesion of synthetic onlays or inlays to the cornea, drug delivery devices, and as anti-adhesion barriers to prevent post-surgical adhesions. Conventional tissue adhesives are generally not suitable for a wide range of adhesive applications. For example, cyanoacrylate-based adhesives have been used for topical wound closure, but the release of toxic degradation products limits their use for internal applications. Fibrin-based adhesives are slow curing, have poor mechanical strength, and pose a risk of viral infection. Additionally, fibrin-based adhesives do not bond covalently to the underlying tissue.
Several types of hydrogel tissue adhesives have been developed, which have improved adhesive and cohesive properties and are nontoxic. These hydrogels are generally formed by reacting a component having nucleophilic groups with a component having electrophilic groups that are capable of reacting with the nucleophilic groups of the first component, to form a crosslinked network via covalent bonding. A number of these hydrogel tissue adhesives are prepared using an oxidized polysaccharide containing aldehyde groups as one of the reactive components (see for example, Kodokian et al., copending and commonly owned U.S. Patent Application Publication No. 2006/0078536, Goldmann, U.S. Patent Application Publication No. 2005/0002893, and Nakajima et al., U.S. Patent Application Publication No. 2008/0319101). However, the instability of oxidized polysaccharides in aqueous solution limits their shelf-life for commercial use. For example, dextran aldehyde undergoes hydrolytic depolymerization much more rapidly than its parent polymer, dextran (E. Schacht et al. J. Controlled Release, 1:33-46, 1984; and Callant at al. Reactive Polymers, 8:129-136, 1988).
Therefore, the need exists for a polymer containing aldehyde groups, which is useful in forming hydrogel tissue adhesives and sealants for medical use and which is more stable in aqueous solution than oxidized polysaccharides. The need also exists for a polymer containing aldehyde groups, which is more stable in aqueous solution than oxidized polysaccharides and which, when combined with a water-dispersible multi-arm polyether amine, produces tissue adhesives with adhesive strengths that are similar to or greater than those of comparable formulations produced with an oxidized polysaccharide.